Sustained Release Monoeximic Formulations of Opioid and Nonopioid Analgesics

Abstract

The present invention relates to monoeximic solid dosage forms for administering pharmaceutical agents, particularly Hydrocodone and acetaminophen, methods for preparing said dosage forms, and methods for providing therapeutic agents to patients in need of treatment.

What is claimed is: 
     
         1 . A sustained release monoeximic dosage form comprising:
 a single rate controlling mechanism,   a therapeutically effective amount of hydrocodone or an acceptable salt thereof and a therapeutically effective amount of acetaminophen,   wherein the amount of acetaminophen is between about 20 and about 40 times by weight of hydrocodone bitartrate or an equivalent amount of another acceptable salt or free base of hydrocodone thereof, and   wherein said dosage form is suitable for twice daily oral dosing to a human, and further wherein said dosage form, when administered to a population of healthy human volunteers, is capable of providing analgesia for at least about 12 hours and produces a plasma profile characterized by:   a mean AUC for hydrocodone from about 11.3 to about 18.7 ng*hr/mL per mg of hydrocodone bitartrate and a mean AUC for acetaminophen from about 28.7 to about 53.5 ng*hr/mL per mg of acetaminophen after a single dose, and   a Cmax for hydrocodone of between about 0.6 ng/mL per mg of hydrocodone bitartrate to about 1.4 ng/mL per mg of hydrocodone bitartrate, and   a Cmax for acetaminophen of between about 2.8 ng/mL per mg of acetaminophen and 7.9 ng/mL/mg of acetaminophen after a single dose.   
     
     
         2 . The sustained release monoeximic dosage form of  claim 1 , wherein the single rate controlling mechanism comprises at least one pharmaceutically acceptable hydrophobic rate controlling material, a pharmaceutically acceptable hydrophilic rate controlling material, a non-polymer rate controlling material or any combinations thereof. 
     
     
         3 . The sustained release monoeximic dosage form of  claim 1 , wherein the dosage form is capable of reducing pain intensity in a patient within about 1 hour. 
     
     
         4 . The sustained release monoeximic dosage form of  claim 3 , wherein the dosage form releases at least 90% of the hydrocodone and acetaminophen in vitro within 12 hours. 
     
     
         5 . The sustained release monoeximic dosage form of  claim 3 , wherein the dosage form releases at least 90% of the hydrocodone and acetaminophen in vitro within about 8 hours. 
     
     
         6 . The sustained release monoeximic dosage form of  claim 1 , wherein the dosage form is adapted to release about 19% to 49% of the hydrocodone and acetaminophen in vitro within 0.75 hours. 
     
     
         7 . The sustained release monoeximic dosage form of  claim 6 , wherein the dosage form releases at least 90% of the hydrocodone and acetaminophen within 12 hours. 
     
     
         8 . The sustained release monoeximic dosage form of  claim 6 , wherein the dosage form releases at least 90% of the hydrocodone and acetaminophen within about 8 hours. 
     
     
         9 . The sustained release monoeximic dosage form of  claim 1 , wherein the healthy human volunteers are residents of North America. 
     
     
         10 . The sustained release monoeximic dosage form of  claim 1 , wherein the dosage form comprises about 500 mg of acetaminophen and about 15 mg of hydrocodone bitartrate. 
     
     
         11 . The sustained release monoeximic dosage form of  claim 1 ,
 wherein the human in which the AUC and Cmax for both hydrocodone and acetaminophen is measured is a non-poor CYP2D6 metabolizer, and   wherein the dosage form produces a Cmax for hydromorphone in the human of between about 0.12 ng/ml and about 0.35 ng/ml after a single dose of 30 mg of hydrocodone bitartrate.   
     
     
         12 . The sustained release monoeximic dosage form of  claim 1 , wherein the plasma concentration for hydrocodone 12 hours after a single 30 mg dose of hydrocodone bitartrate is between about 11.0 ng/ml and about 27.4 ng/ml. 
     
     
         13 . The sustained release monoeximic dosage form of  claim 12 , wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μg/ml and about 2.5 μg/ml. 
     
     
         14 . The sustained release monoeximic dosage form of  claim 1 , wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μg/ml and about 2.5 μg/ml. 
     
     
         15 . The sustained release monoeximic dosage form of  claim 1 , wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 6.4 hours and about 19.6 hours. 
     
     
         16 . The sustained release monoeximic dosage form of  claim 1 , wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 8.4 hours and about 19.6 hours. 
     
     
         17 . The sustained release monoeximic dosage form of  claim 1 , wherein after a single dose of 1000 mg of acetaminophen, the plasma concentration profile exhibits a width at half height for acetaminophen of between about 0.8 hours and about 12.3 hours.